J. Crayton Pruitt Family Department of Biomedical Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL, 32611, USA.
Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, 32603, USA.
Macromol Biosci. 2023 Sep;23(9):e2300237. doi: 10.1002/mabi.202300237. Epub 2023 Jul 9.
Macrophages modulate the wound healing cascade by adopting different phenotypes such as pro-inflammatory (M1) or pro-wound healing (M2). To reduce M1 activation, the JAK/STAT pathway can be targeted by using suppressors of cytokine signaling (SOCS1) proteins. Recently a peptide mimicking the kinase inhibitory region (KIR) of SOCS1 has been utilized to manipulate the adaptive immune response. However, the utilization of SOCS1-KIR to reduce pro-inflammatory phenotype in macrophages is yet to be investigated in a biomaterial formulation. This study introduces a PEGDA hydrogel platform to investigate SOCS1-KIR as a macrophage phenotype manipulating peptide. Immunocytochemistry, cytokine secretion assays, and gene expression analysis for pro-inflammatory macrophage markers in 2D and 3D experiments demonstrate a reduction in M1 activation due to SOCS1-KIR treatment. The retention of SOCS1-KIR in the hydrogel through release assays and diffusion tests is demonstrated. The swelling ratio of the hydrogel also remains unaffected with the entrapment of SOCS1-KIR. This study elucidates how SOCS1-KIR peptide in PEGDA hydrogels can be utilized as an effective therapeutic for macrophage manipulation.
巨噬细胞通过采用不同的表型（如促炎（M1）或促伤口愈合（M2））来调节伤口愈合级联反应。为了减少 M1 的激活，可以使用细胞因子信号转导抑制剂（SOCS1）蛋白来靶向 JAK/STAT 途径。最近，一种模拟 SOCS1 激酶抑制区（KIR）的肽已被用于操纵适应性免疫反应。然而，SOCS1-KIR 用于减少巨噬细胞中的促炎表型在生物材料配方中的应用尚未得到研究。本研究引入了 PEGDA 水凝胶平台来研究 SOCS1-KIR 作为一种巨噬细胞表型操纵肽。免疫细胞化学、细胞因子分泌测定以及二维和三维实验中促炎巨噬细胞标志物的基因表达分析表明，SOCS1-KIR 处理可减少 M1 的激活。通过释放试验和扩散试验证明 SOCS1-KIR 在水凝胶中的保留。水凝胶的溶胀比也不受 SOCS1-KIR 包埋的影响。本研究阐明了 PEGDA 水凝胶中的 SOCS1-KIR 肽如何可作为有效的巨噬细胞操纵治疗方法。
